Tailoring interactions for cisPro peptide bond stabilization

Abstract

Elucidation of the nature of non-covalent interactions that govern the rate-limiting cis-trans isomerism at Xaa-Pro peptide bonds is fundamental to unravelling the protein folding mechanism, the stereoelectronic control elements of the structure and dynamics of the peptide bond, and the design of novel peptide isosteres. CisPro rotamers are stabilized by very few interactions compared to the transPro rotamer and are hence relatively scarcely populated. Design of novel interactions that can bias cisPro stability, with least mutations to the prolyl peptide bond, is crucial for accessing the cisPro motif in a variety of peptides. This mini review discusses the various interactions tailored for improving cisPro stability.